Support is requested for a Keystone Symposia meeting entitled The NF-?B System in Health and Disease, organized by Alexander Hoffmann and Louis M. Staudt. The meeting will be held in Keystone, Colorado from February 23 - 28, 2014. NF-?B factors play key roles in diverse physiological and pathological processes, involving innate and adaptive immunity, and many organs and cell types and are regulated through numerous interconnected molecular mechanisms. The NF-?B system refers to the gene regulatory and signal regulatory networks (GRNs and SRNs), within which NF-?B transcription factors exert their activities. Those regulatory networks include mitogen-activated kinases, caspases and other apoptotic and necroptotic regulators, regulators of autophagy, cytoskeletal organization, and proliferation, as well as the interferon-regulatory innate immune network. Indeed, understanding these processes as an interconnected system is paramount to studies of disease, as manifested by complex immunological, inflammatory, and tumor pathologies. To address these complexities and move towards a predictive understanding, this Keystone Symposia meeting will emphasize the consideration of regulatory interactions, quantitative measurements, in silico modeling, and genome scale studies. The meeting will provide an overview of the field and catalyze scientific interactions in the age of Systems Biology to advance post- genomic Immunology.